Direct identification of the Ca 2+ channel small Ca v β 2f subunit in human cardiac ventricular tissue

Ca v β subunits are essential modulators of cardiac L‐type Ca 2+ channels. We have previously cloned Ca v β 2f , a small splice variant of the human cardiac Ca v β 2 subunit (1). Ca v β 2f is unique because it does not contain the α 1c interaction domain and intact membrane‐associated guanylate kinase (MAGUK)‐like module. Yet when expressed in COS1 cells free of endogenous Ca v 1.2 channels, the recombinant CFP‐labeled Ca v β 2f co‐immunoprecipitates with the α 1c subunit, co‐localizes with α 1c to the plasma membrane and facilitates voltage gating of the Ca v 1.2 channel currents similar to conventional Ca v β 2a . Here we report direct identification of Ca v β 2f in human ventricular tissue obtained from autopsy specimens. Using antibody against α 1c , the cardiac Ca v 1.2 channel complex was co‐immunoprecipitated from the microsomal fraction of human left ventricle and characterized in comparison with recombinant Ca v β 2f . The small Ca v β 2f was identified as one of the major Ca v β 2 splice variants of the Ca v 1.2 channel complex. This result indicates that the Ca v β‐subunit modulation of Ca v 1.2 calcium channels in human heart is subject to regulation by alternative splicing of the Ca v β 2 gene and may not need the MAGUK‐like module. Supported by the NIA Intramural Research Program.